Prevalence in Britain of abnormal prion protein in human appendices before and after exposure to the cattle BSE epizootic

O Noel Gill,Katy Sinka,Mark Mccall,David Brown,Nick Andrews,James W Ironside,Sebastian Brandner,Carole Kelly,Peter Bellerby,Philip Edwards,Yvonne Spencer,Jacqueline Linehan,Reza Dabaghian,David A Hilton,Linda M Mccardle,David J Everest,Simon Mead,Angela Richard-Loendt,Marion Simmons

doi:10.1007/s00401-020-02153-7

Abstract

Widespread dietary exposure of the population of Britain to bovine spongiform encephalopathy (BSE) prions in the 1980s and 1990s led to the emergence of variant Creutzfeldt-Jakob Disease (vCJD) in humans. Two previous appendectomy sample surveys (Appendix-1 and -2) estimated the prevalence of abnormal prion protein (PrP) in the British population exposed to BSE to be 237 per million and 493 per million, respectively. The Appendix-3 survey was recommended to measure the prevalence of abnormal PrP in population groups thought to have been unexposed to BSE. Immunohistochemistry for abnormal PrP was performed on 29,516 samples from appendices removed between 1962 and 1979 from persons born between 1891 through 1965, and from those born after 1996 that had been operated on from 2000 through 2014. Seven appendices were positive for abnormal PrP, of which two were from the pre-BSE-exposure era and five from the post BSE-exposure period. None of the seven positive samples were from appendices removed before 1977, or in patients born after 2000 and none came from individuals diagnosed with vCJD. There was no statistical difference in the prevalence of abnormal PrP across birth and exposure cohorts. Two interpretations are possible. Either there is a low background prevalence of abnormal PrP in human lymphoid tissues that may not progress to vCJD. Alternatively, all positive specimens are attributable to BSE exposure, a finding that would necessitate human exposure having begun in the late 1970s and continuing through the late 1990s.

Highlights

The dietary exposure of the population of Britain to bovine spongiform encephalopathy (BSE) prions in the late 1980s and early 1990s [45] led to the emergence of variant Creutzfeldt-Jakob Disease [48]
A highly characteristic feature of variant Creutzfeldt-Jakob Disease (vCJD) is the accumulation of abnormal prion protein, a misfolded form of the normal host prion protein (PrPC) [2] in the lymphoreticular system, such as lymph nodes, tonsils, spleen and lymphoid follicles in intestinal organs [19, 21, 24], something that is absent in sporadic CJD [19, 21], or other transmitted forms such as kuru [6, 10] or iatrogenic CJD [18]
The presence of abnormal PrP in lymphoreticular tissues precedes involvement of the central nervous system (CNS) [5, 22] and it was inferred that the prevalence of vCJD carrier status in the population could be estimated through testing appendix and tonsil specimens removed at elective operations

Summary

Introduction

The dietary exposure of the population of Britain to bovine spongiform encephalopathy (BSE) prions in the late 1980s and early 1990s [45] led to the emergence of variant Creutzfeldt-Jakob Disease (vCJD) [48]. This form of prion disease is characterised by a strain that is different from other forms of human prion disease [20], giving rise to a distinct clinical picture, biochemical pattern [9] and histopathological appearance [48]. A number of studies have been conducted to improve the accuracy of vCJD abnormal PrP prevalence estimates [7, 11, 15]

Methods

Results

Conclusion